Glioblastoma
Conditions
Keywords
Glioblastoma Multiforme, Avastin, Brain Cancer, GBM
Brief summary
This is a Phase II, open-label, multicenter, randomized, non comparative study consisting of two concurrent single-arms. Approximately 160 subjects will be randomized in a 1:1 ratio to Arm 1 (bevacizumab alone) or Arm 2 (bevacizumab + irinotecan).
Interventions
DRUGbevacizumab
Intravenous repeating dose
DRUGirinotecan
Intravenous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * Age ≥ 18 years * Histologically confirmed GBM in first or second relapse * Radiographic demonstration of disease progression following prior therapy * Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to first treatment (Day 0) * An interval of ≥ 4 weeks since prior surgical resection * Prior standard radiation for GBM * Prior chemotherapy: first-relapse subjects * Prior chemotherapy: second-relapse subjects * Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 2 weeks from vincristine); 4 weeks from any investigational agent; 1 week from non-cytotoxic agents; 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field * Prior therapy with gamma knife or other focal high-dose radiation is allowed but the subject must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field * Karnofsky performance status ≥ 70 * Life expectancy \> 12 weeks * Use of an effective means of contraception in males and in females of childbearing potential * Ability to comply with study and follow-up procedures
Exclusion criteria
* Prior treatment with irinotecan, bevacizumab, or another VEGF or VEGFR-targeted agent * Prior treatment with prolifeprospan 20 with carmustine wafer * Prior intracerebral agents * Need for urgent palliative intervention for primary disease (e.g., impending herniation) * Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: Presence of hemosiderin; Resolving hemorrhagic changes related to surgery; Presence of punctate hemorrhage in the tumor * Received more than two treatment regimens for Grade III and/or Grade IV glioma * Blood pressure of \> 150 mmHg systolic and \> 100 mmHg diastolic * History of hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater CHF * History of myocardial infarction or unstable angina within 6 months prior to Day 0 * History of stroke or transient ischemic attack within 6 months prior to study enrollment * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 0 * Evidence of bleeding diathesis or coagulopathy * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * History of intracerebral abscess within 6 months prior to Day 0 * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 0 * Serious non-healing wound, ulcer, or bone fracture * Pregnancy (positive pregnancy test) or lactation * Known hypersensitivity to any component of bevacizumab * History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix) * Pregnant or nursing females * Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication * Subjects unable to undergo an MRI with contrast
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response, as determined by the independent review facility (IRF) | Complete response or partial response, determined on two consecutive assessments ≥4 weeks apart |
| Progression-free survival, as determined by the IRF | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of adverse events and serious adverse events | Length of patient on study |
| Duration of objective response, as determined by the IRF | Complete or partial response determined on two consecutive assessments ≥4 weeks apart |
| Overall survival | Time from randomization to death |
Outcome results
None listed